Galectin-9 regulates HTR8/SVneo function via JNK signaling

Area of Science:

• Reproductive Immunology
• Cell Biology

Background:

• Successful pregnancy requires trophoblasts to establish immune tolerance and adequate placental function.
• Inadequate placental perfusion is linked to pregnancy complications.
• Galectin-9 (Gal-9) is known for its immunomodulatory roles in various physiological and pathological processes.

Purpose of the Study:

• To investigate the effects of Gal-9 on human first-trimester extravillous trophoblast cells (HTR8/SVneo).
• To explore Gal-9's role in regulating trophoblast apoptosis, cytokine production, and angiogenesis.
• To determine Gal-9's potential involvement in spontaneous abortion.

Main Methods:

• Utilized immortalized human first-trimester extravillous trophoblast cells (HTR8/SVneo).
• Assessed the impact of Gal-9 on cell apoptosis, cytokine profiles (IFN-γ, IL-17A, IL-4), and angiogenesis.
• Investigated the interaction with Tim-3 and the involvement of JNK signaling pathways.
• Correlated Gal-9 levels with spontaneous abortion cases.

Main Results:

• Gal-9 inhibited apoptosis and the production of pro-inflammatory cytokines (IFN-γ, IL-17A) in HTR8/SVneo cells.
• Gal-9 promoted the production of IL-4 and enhanced crosstalk with endothelial cells via Tim-3.
• Gal-9's effects were dependent on JNK signaling.
• Lower Gal-9 levels were associated with spontaneous abortion.

Conclusions:

• Gal-9 regulates trophoblast cell functions, including apoptosis, cytokine production, and angiogenesis, through the Tim-3/JNK pathway.
• Gal-9 is essential for maintaining normal pregnancy and may serve as a biomarker for recurrent pregnancy loss.
• Targeting Gal-9 could offer a novel therapeutic strategy for pregnancy loss.